E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of brodalumab, (210 mg every 2 weeks (Q2W); and 140 mg Q2W) compared to placebo, in subjects with psoriatic arthritis, as measured by the proportion of subjects achieving an American College of Rheumatology (ACR) 20 response at week 16. |
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objectives:
To evaluate the efficacy of brodalumab compared to placebo on the following:
Psoriasis Area and Severity Index (PASI) 75 at week 16
Van der Heijde modified Total Sharp score (mTSS) at week 24 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Brodalumab Pharmacokinetic Substudy Objective (optional): To characterize the pharmacokinetics of brodalumab
Biomarker development and pharmacogentic substudy (optional):
Objective: to collect samples for biomarker analysis; to investigate the effects of genetic variation in disease genes and drug target genes on psoriatic arthritis and/or subject response to brodalumab |
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E.3 | Principal inclusion criteria |
- Subject has provided informed consent
- Subject is ≥ 18 years of age at time of screening
- Subject has had a diagnosis of psoriatic arthritis for at least 6 months and currently meets the CASPAR criteria
- Subject has ≥ 3 tender and ≥ 3 swollen joints
- Subject has a history of intolerance or inadequate response to NSAIDs and/or DMARDs for psoriatic arthritis |
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E.4 | Principal exclusion criteria |
Other Medical Conditions:
- Subject has any systemic disease (eg, renal failure, heart failure, hypertension, liver disease, diabetes, anemia) considered by the investigator to be clinically significant and uncontrolled.
- Subject has any concurrent medical condition or electrocardiogram (ECG) abnormality that, in the opinion of the investigator, could cause this study to be detrimental to the subject.
Washouts or Other Treatments
- Subject has used commercially available or investigational biologic therapies for psoriasis and/or psoriatic arthritis as follows:
anti-tumor necrosis factor (TNF) therapy within 2 months prior to investigational product initiation
other experimental or commercially available biologic therapies for psoriasis and/or psoriatic arthritis within 3 months prior to investigational product initiation
anti-IL17 or anti-IL12/IL23 biologic therapy, including brodalumab, secukinumab, ixekizumab, ustekinumab, briakinumab at any time
rituximab at any time
General
- Subject is currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s) prior to screening.
- Other investigational procedures while participating in this study are excluded.
- Subject has known sensitivity to any of the products or components to be administered during dosing.
-Subject has a history or evidence of suicidal ideation (severity of 4 or 5) or any suicidal behavior based on an assessment with the Columbia Suicide Severity Rating Scale (eC-SSRS) at screening or at baseline
-Subject has a history or evidence of a psychiatric disorder or substance abuse that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
-Subject has severe depression based on a total score of ≥ 15 on the Patient Health Questionnaire-8 (PHQ-8) at screening or baseline (note: subjects with a total score of 10-14 on the PHQ-8 should referred to a mental health professional).
- Women of reproductive potential who are not willing to use an acceptable form of birth control during the study and for an additional 8 weeks after the last dose of study drug.
- Women who are lactating/breastfeeding or planning to breastfeed during the study and for an additional 8 weeks after the last dose of Amgen study drug.
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E.5 End points |
E.5.1 | Primary end point(s) |
ACR20 response at week 16 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key secondary Endpoints:
PASI 75 at week 16
mTSS change from baseline at week 24 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PASI 75 at week 16
mTSS change from baseline at week 24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
randomized, double-blind, placebo-controlled study with long term extension |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 71 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
Czech Republic |
France |
Greece |
Hungary |
Italy |
Mexico |
Netherlands |
Poland |
Russian Federation |
Spain |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |